To demonstrate an etiologic agent in rheumatoid arthritis (RA), we have cocultivated rheumatoid synovial cells with human embryo lung cells or fetal rabbit synovial cells, and for the first time consistently observed viral particles by electron microscopy in these cocultivations. Inoculation of cocultivation extracts into the brain of suckling mice produces severe pathology and death in the mice with recovery of virus titers of 10 to the third power - 10 to the fourth power lethal mouse brain doses per ml of infected mouse brain homogenate. Our objectives are to confirm the presence of the virus in the rheumatoid synovial cells, to obtain sufficient virus titers for characterization of the agent, and to demonstrate its relevance to the etiology of RA. We propose to: 1) increase the titer of the virus preparations by repeated passage in mouse brain; 2) detect a cell line in which the virus replicates so that the titer can be increased and the virus more easily purified; 3) produce an antiserum in rabbits to the mouse brain virus material for testing by indirect immunofluorescence on rheumatoid and nonrheumatoid synovial cells; 4) titer the virus by hemagglutination tests and/or counterimmunoelectrophoresis; 5) study the virus-host cell model with respect to parameters that have been used to characterize the abnormal traits of rheumatoid synovial cells in culture: altered lysomal hydrolase content, altered protease production, increased synthesis of hyaluronic acid, and increased production of a growth inhibitor. We will also attempt to develop an animal model of RA by injection of the viral material into rabbit joints; we willl then carry out virologic, histologic, and biochemical studies on the infected and contralateral uninjected joints while observing the rabbits for weeks and months.